Biomedical subjects

Rui Sun

Publications and source records attributed to Rui Sun.

At least 19 recordsLinked to original sources

PubMed2026

The impact for causal associations between common diseases and inflammatory bowel disease: a disease-wide bidirectional Mendelian randomization study.

OBJECTIVES: Observational studies on associations between various diseases and inflammatory bowel disease (IBD) are often limited by confounding and reverse causation. We aimed to assess potential causal relationships between a wide range of diseases and IBD, including Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We performed a comprehensive bidirectional Mendelian randomization (MR) analysis of 104 common diseases and IBD traits using the generalized summary-data-based MR (GSMR) approach. Genome-wide association study (GWAS) summary statistics for diseases were obtained from the MRC Integrative Epidemiology Unit, and IBD data from the International IBD Genetics Consortium. Summary-data-based MR (SMR) integrating GWAS and expression quantitative trait locus data was applied to identify pleiotropic genes associated with IBD. RESULTS: MR analyses identified 38, 34, and 52 exposures significantly associated with IBD, UC, and CD, respectively. Childhood- and adult-onset asthma showed distinct causal effects on UC and CD. Reverse MR indicated associations between IBD traits and 15 diseases, including multiple sclerosis. SMR identified RGS14 and CARD9 as pleiotropic genes linked to IBD, suggesting shared genetic mechanisms with asthma and multiple sclerosis. CONCLUSIONS: These findings provide evidence for causal links and shared immune-related genetic mechanisms underlying IBD, highlighting potential targets for future research.

Humans↗

PubMed2026

AI proteomics: from protein identification to virtual cells.

Artificial intelligence (AI) is transforming scientific research, including proteomics. In this Perspective, we highlight key mass spectrometry (MS)-based proteomics areas where AI is driving innovation, ranging from protein identification to building AI virtual cells. These include improving peptide and protein identification and quantification; characterizing protein-protein interactions and protein complexes; advancing spatial and perturbation proteomics; integrating multi-omics data; and, ultimately, enabling AI virtual cells. Finally, we call for global collaboration among data producers, data consumers and other stakeholders to establish an AI-friendly ecosystem for MS-based proteomics, laying the foundation for transformative advancements in proteomics driven by AI.

Proteomics↗

PubMed2026

Decoding glioblastoma evolution and heterogeneity through mechanistic modeling: implications for clinical translation.

Glioblastoma (GBM) is one of the most aggressive and lethal primary brain tumors in adults, characterized by dynamic clonal evolution and extensive genomic, cellular, spatial, and microenvironmental heterogeneity. Multi-omics studies have revealed that GBM follows complex evolutionary trajectories involving genetic, epigenetic, transcriptional, and immune-microenvironmental remodeling as tumors grow, adapt to the brain microenvironment, and acquire therapeutic resistance. Increasing evidence suggests that GBM may originate from aberrant neural stem or progenitor cells, including those residing in the subventricular zone, and that glioblastoma stem cells (GSCs) contribute to tumor propagation, heterogeneity, and recurrence. A key conceptual challenge is to reconcile hierarchical cancer stem cell models, in which GSCs are viewed as relatively stable tumor-propagating subpopulations, with dynamic state plasticity models, in which stem-like properties can be reversibly acquired or lost during transitions among proneural-like, mesenchymal-like, invasive, and therapy-tolerant states. Recent advances in single-cell profiling, spatial transcriptomics, lineage tracing, organoid culture, 3D bioprinting, genetically engineered models, and artificial intelligence (AI)-assisted computational modeling have substantially improved the ability to study these processes. However, no currently available model fully recapitulates human GBM heterogeneity, recurrence, treatment history, and tumor-microenvironment interactions. Therefore, model selection should be guided by clearly defined mechanistic questions rather than by reliance on any single platform. This review summarizes current advances in in vitro, ex vivo, in vivo, and computational models for studying GBM evolution and heterogeneity, and discusses how integrated model pipelines may improve preclinical drug testing, treatment-response prediction, and precision neuro-oncology.

Humans↗

PubMed2026

Allelic variation in UVR8 modulates thermotolerance-yield tradeoffs in plants.

Industrial activities have driven stratospheric ozone depletion, increasing surface UV-B radiation while exacerbating global warming. These changes limit crop productivity, alter species distributions, and disrupt plant metabolic processes, but the mechanisms linking energy signaling to heat-stress responses remain unclear. Here, we identify the photoreceptor UV RESISTANCE LOCUS 8b (OsUVR8b) as a substrate of SNF1-related protein kinase 1 (SnRK1) in rice and reveal a natural variation at its SnRK1-mediated phosphorylation site (Ser177) that is correlated with adaptation to tropical climates. The thermotolerant OsUVR8bAla177 accessions show geographic enrichment in low-latitude regions with elevated temperatures. Functional validation through prime editing demonstrated that a Ser177-to-Ala177 substitution enhances heat tolerance, whereas the reverse edit compromises it. Mechanistically, OsUVR8bSer177 exhibits reduced stability and an impaired capacity for scavenging reactive oxygen species under heat stress. The regulatory function of the OsUVR8b Ser177 phosphorylation site, a molecular switch that governs UVR8 stability and thermotolerance, can be functionally re-established across rice, Arabidopsis, tobacco, and soybean, indicating its preservation during domestication. Notably, OsUVR8bSer177 maintains higher fertility and yield under non-stress conditions, indicating a tradeoff between heat adaptation and productivity. Our findings thus establish this switch as a key regulator of the yield-resilience balance and a promising target for breeding of climate-resilient crops.

Thermotolerance↗

PubMed2006

Human prolactin promotes human secondary immunoglobulin response in human/SCID mouse chimeras.

Recombinant human prolactin (rhPRL) was administered to huPBL-SCID mice to determine its effects on production of human immunoglobulin (Ig). The huPBL-SCID mice were injected intraperitoneally (i.p.) with 10 mug rhPRL every other day for a total of 10 injections. The results reconfirmed that rhPRL significantly increased the numbers of human CD3+ T cells and human CD19+ B cells in spleens, lymph nodes, and thymuses of huPBL-SCID mice. The huPBL-SCID mice were then concurrently given various doses of diphtheria-tetanus (DT) vaccine and 10-mug i.p. injections of rhPRL and were examined for the presence of human DT-specific proliferation of lymph node cells in vitro and antibody production in vivo. rhPRL greatly improved the engraftment of functional human lymphocytes (CD3+ T cells and CD19+ B cells) in DT-immunized huPBL-SCID mice. The rhPRL-treated, DT-immunized huPBL-SCID mice produced significantly larger amounts of DT-specific antibodies in response to the vaccine. The predominant Ig isotype induced after immunization was IgG. Thus, rhPRL stimulation promotes human secondary IgG responses in huPBL-SCID mice.

Animals↗

PubMed2006

Reverse of NK cytolysis resistance of type II cytokine predominant-human tumor cells.

Tumor cells suppress host immunity by secreting soluble factors, among which cytokines play important roles. Type I cytokine mRNA levels (IL-2 and IFNgamma) and type II cytokine mRNA levels (IL-4, IL-10 and IL-13) of twenty tumor cell lines and fresh tumor tissues from fifteen patients with colorectal cancer were examined by RT-PCR method. Upon analysis, tumor cells showed type II predominance and were resistant to NK cytolysis. In order to reverse the type II predominant status, type I cytokines (IL-2 or IFNgamma) and/or anti-type II cytokine antibody (IL-10 mAb) were used in an in vitro study. By this shifting treatment, type II cytokine mRNA levels of these tumor cells were decreased, moreover, the sensitivity to natural cytolysis of these cells was then significantly increased. Thus, tumor-induced type II cytokine dominance is possibly to be shifted into type I status, which benefits the anti-tumor natural immunity.

Adenocarcinoma↗

PubMed2006

Pre-activation of T lymphocytes by low dose of concanavalin A aggravates toll-like receptor-3 ligand-induced NK cell-mediated liver injury.

Concanavalin A (Con A), a widely used murine T cell stimulator, could induce T cell-mediated hepatitis when used in an abundant dosage. However, the immune-modulating role of non-hepatotoxic dosage of Con A in hepatic immune responses remains obscure. In order to evaluate the effect of non-hepatotoxic Con A on hepatic NK cells, pretreatment of mice with low dose of Con A was performed on polyinosinic-polycytidylic acid (poly I:C) [toll-like receptor-3 (TLR-3) ligand]-induced NK cell-mediated hepatitis. The role of the Con A-pre-activated T cells in NK cell function was then determined. The results demonstrated that Con A pretreatment aggravated poly I:C-induced liver injury with elevation of serum transaminases, hepatic necrosis and serum IFN-gamma level. In parallel to the enhanced accumulation of activated NK cells into liver, the natural cytotoxicity and IFN-gamma production by hepatic NK cells were significantly augmented. Moreover, depletion of T cells suppressed the aggravating effect of Con A pretreatment. Collectively, the aggravation of poly I:C-induced hepatitis by Con A pretreatment may be due to the generation of more vigorous NK cells which is dependent on the presence of T cells. This investigation will help to explain the synergistic effects of NK and T cells in liver inflammatory injury.

Animals↗

PubMed2006

Interleukin-15 prevents concanavalin A-induced liver injury in mice via NKT cell-dependent mechanism.

Administration of concanavalin A (Con A) induces a rapid and severe liver injury in mice. Natural killer T (NKT) cells are recognized to be the key effector cells, and a variety of cytokines [e.g., interleukin 4 (IL-4), IL-5, interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha)] have been shown to play vital roles in Con A-induced liver injury, whereas the role of IL-15, a critical cytokine in the development and homeostasis of NKT cells, remains obscure. In this study, pretreatment with IL-15 prevented mice from Con A-induced mortality, elevation of serum transaminase, liver necrosis, and hepatocyte apoptosis. Depletion of NKT cells abolished Con A-induced liver injury, which could be restored by adoptive transfer of purified NKT cells but not by that of in vivo or in vitro IL-15-treated hepatic NKT cells. Furthermore, transfer of wild-type NKT cells to CD1d-/- mice restored liver injury, whereas transfer of IL-15-treated NKT cells did not. IL-15 pretreatment decreased the NKT-derived IL-4, IL-5, and TNF-alpha production, thereby resulting in less infiltration of eosinophils, which play a critical role in Con A-induced liver injury. In conclusion, IL-15 protects against Con A-induced liver injury via an NKT cell-dependent mechanism by reducing their production of IL-4, IL-5, and infiltration of eosinophils. These findings suggest that IL-15 may be of therapeutic relevance in human autoimmune-related hepatitis.

Animals↗

PubMed2006

STAT1 contributes to dsRNA inhibition of liver regeneration after partial hepatectomy in mice.

Increasing evidence suggests that liver regeneration is suppressed in patients with chronic HCV infection; however, the underlying mechanisms remain unclear. Previously, we demonstrated that injection of the synthetic double-stranded RNA (dsRNA) poly I:C to mimic viral infection suppresses liver regeneration in the partial hepatectomy (PHx) model, whereby IFN-gamma contributes to the inhibition. In this study, we examined the role of the IFN-gamma-activated downstream signal (STAT1) and genes (IRF-1, p21(cip1), and SOCS1) in liver regeneration and hepatocyte proliferation. Results show that disruption of the STAT1 gene abolished poly I:C suppression of liver regeneration and the inhibitory effect of poly I:C on liver regeneration was diminished in IRF-1(-/-) and p21(cip1-/-)mice. Treatment with IFN-gamma in vitro inhibited cell proliferation of wild-type mouse hepatocytes, but not STAT1(-/-) hepatocytes. The inhibitory effect of IFN-gamma on cell proliferation was also diminished in IRF-1(-/-) and p21(cip1-/-) hepatocytes, but enhanced in SOCS1(-/-) hepatocytes. Hepatocyte proliferation was unaffected by treatment with poly I:C alone, but when hepatocytes were co-cultured with liver lymphocytes, proliferation was inhibited by IFN-gamma/STAT1-dependent mechanisms. Moreover, in HCV-infected livers with cirrhosis, activation of STAT1 was detected and correlated positively with liver injury (elevated serum levels of AST) but negatively with hepatocyte proliferation (hepatocyte PCNA and Ki-67 positive immunostaining). In conclusion, STAT1 is involved in dsRNA suppression of liver regeneration; not only does STAT1 activation contribute to liver injury, it may also block liver repair through inhibition of hepatocyte proliferation in HCV-infected patients, playing an important role in the pathogenesis of disease.

Animals↗

PubMed2006

Rapid separation of four main taxoids in Taxus species by a combined LLP-SPE-HPLC (PAD) procedure.

A method is described for the simultaneous determination of paclitaxel and three related taxoids, 10-deacetylbaccatin III (10-DAB III), baccatin III, and cephalomannine, in the extracts from the needles of three Chinese yew species, Taxus cuspidata, T. chinensis, and T. media. SPE was applied as the sample preparation technique and RP-HPLC with a photodiode array detector (PAD) was used for the analysis of extract samples. The crude extracts were treated with an improved SPE cartridge packed with a combination of 1-vinyl-pyrrolidin-2-one and divinyl-benzene. The eluent was 75% methanol. The following separation was achieved with a gradient program on an HIQ SIL C18W column in a system of ACN/water within 60 min. The samples were detected by PAD at wavelengths of 232.1 nm for 10-DAB III, 229.8 nm for baccatin III and paclitaxel, and 223.9 nm for cephalomannine. The content of 10-DAB III, baccatin III, cephalomannine, and paclitaxel varied from 0.0277 to 0.0875, 0.0254 to 0.0405, 0.0715 to 0.2486, and 0.0996 to 0.1301 mg/g in fresh needles of the above yew species, respectively. The assay achieved good resolution in the separation between the four compounds, and it can be used for quality control or purity determination for those in bulk and pharmceutical dosage forms.

Alkaloids↗

PubMed2006

Natural killer cells ameliorate liver fibrosis by killing activated stellate cells in NKG2D-dependent and tumor necrosis factor-related apoptosis-inducing ligand-dependent manners.

BACKGROUND & AIMS: Viral hepatitis infection, which is a major cause of liver fibrosis, is associated with activation of innate immunity. However, the role of innate immunity in liver fibrosis remains obscure. METHODS: Liver fibrosis was induced either by feeding mice with the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet or by injecting them with carbon tetrachloride. The Toll-like receptor 3 ligand, polyinosinic-polycytidylic acid, was used to activate innate immunity cells and mediators, including natural killer cells and interferon gamma. RESULTS: In the mouse model of DDC-induced liver fibrosis, natural killer cell activation by polyinosinic-polycytidylic acid induced cell death to activated hepatic stellate cells and attenuated the severity of liver fibrosis. Polyinosinic-polycytidylic acid treatment also ameliorated liver fibrosis induced by carbon tetrachloride. The observed protective effect of polyinosinic-polycytidylic acid on liver fibrosis was diminished through either depletion of natural killer cells or by disruption of the interferon gamma gene. Expression of retinoic acid early inducible 1, the NKG2D ligand, was undetectable on quiescent hepatic stellate cells, whereas high levels were found on activated hepatic stellate cells, which correlated with the resistance and susceptibility of quiescent hepatic stellate cells and activated hepatic stellate cells to natural killer cell lysis, respectively. Moreover, treatment with polyinosinic-polycytidylic acid or interferon gamma enhanced the cytotoxicity of natural killer cells against activated hepatic stellate cells and increased the expression of NKG2D and tumor necrosis factor-related apoptosis-inducing ligand on liver natural killer cells. Blocking NKG2D or tumor necrosis factor-related apoptosis-inducing ligand with neutralizing antibodies markedly diminished the cytotoxicity of polyinosinic-polycytidylic acid-activated natural killer cells against activated hepatic stellate cells. CONCLUSIONS: Our findings suggest that natural killer cells kill activated hepatic stellate cells via retinoic acid early inducible 1/NKG2D-dependent and tumor necrosis factor-related apoptosis-inducing ligand-dependent mechanisms, thereby ameliorating liver fibrosis.

Animals↗

PubMed2006

Selective elimination of hepatic natural killer T cells with concanavalin A improves liver regeneration in mice.

BACKGROUND: Although concanavalin A (Con A) as a T cell stimulant can cause natural killer T (NKT) cell-mediated liver injury in mice and a nonhepatotoxic dose of Con A can trigger innate immune cells including NKT cells to prevent tumor metastasis in the liver, little is known about the role of Con A-primed NKT cells in liver repair. In this study, we aimed to investigate the effect of pretreatment with a nontoxic dose of Con A on subsequent liver regeneration in mice. METHODS: A nontoxic dose of Con A was injected intravenously 24 h before partial hepatectomy (PHx), which was used as a model of liver regeneration. Ratios of remnant liver mass to body weight, bromodeoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) labeling were used to assess liver regeneration. RESULTS: Hepatic mononuclear cells were isolated and analyzed by flow cytometry. After PHx, the ratios of liver weight to body weight, PCNA-positive hepatocytes and BrdU-positive hepatocytes in Con A-pretreated mice were significantly higher than that of phosphate-buffered saline-treated mice, indicating that Con A pretreatment can accelerate liver regeneration. Flow cytometric analysis showed that NKT cells were significantly activated and selectively eliminated after the Con A administration. Moreover, NKT cells expressed more apoptosis-related molecules, Fas and Annexin V. CONCLUSIONS: Taken together, Con A accelerates liver regeneration in mice by eliminating hepatic NKT cells via activation-induced cell death.

Alanine Transaminase↗

PubMed2006

Chronic ethanol consumption inhibits hepatic natural killer cell activity and accelerates murine cytomegalovirus-induced hepatitis.

BACKGROUND: Chronic alcohol drinking accelerates the progression of liver disease in patients with hepatitis viral infection; however, the underlying mechanisms are not fully understood. METHODS: Here, we examined the effects of chronic ethanol feeding on hepatic natural killer (NK) cells and liver injury in 2 murine models of liver injury: injection of synthetic double-stranded RNA polyinosinic-polycytidylic acid (poly I:C), which mimics viral infection, and infection with murine cytomegalovirus (MCMV). Mice were fed the Lieber-DeCarli liquid diet containing 5% (vol/vol) ethanol for 8 weeks, resulting in a significant decrease in the percentage and total number of NK cells in the liver. RESULTS: In control, pair-fed mice, poly I:C injection induced NK cell accumulation in the liver and activated hepatic NK cell cytotoxicity, whereas such induction and activation were diminished in ethanol-fed mice. Treatment with poly I:C also induced expression of NKG2D, granzyme B, perforin, Fas L, TRAIL, and IFN-gamma on liver lymphocytes, which were delayed or reduced in ethanol-treated mice compared with pair-fed mice. In contrast, chronic ethanol feeding did not affect poly I:C-induced mild liver injury. Furthermore, MCMV infection activated hepatic NK cells and induced hepatic inflammation and injury. Chronic ethanol consumption inhibited hepatic NK cell activation during MCMV infection, but enhanced MCMV-induced liver injury, viral titer, and inflammation in the liver. CONCLUSIONS: Taken together, these findings suggest that chronic ethanol consumption decreases hepatic NK activity, thereby accelerating MCMV-induced hepatitis and liver injury.

Alanine Transaminase↗

PubMed2006

Human interleukin-15 improves engraftment of human T cells in NOD-SCID mice.

Human nonobese diabetic-severe combined immune deficiency (NOD-SCID) mouse chimeras have been widely used as an in vivo model to assess human immune function. However, only a small fraction of transferred human T lymphocytes can be detected in human peripheral blood lymphocyte (huPBL)-NOD-SCID chimeras. To improve the reconstitution of human T lymphocytes in NOD-SCID mice, the use of recombinant human interleukin-15 (rhIL-15) as a stimulator of human lymphocytes was explored. Administration of rhIL-15 after transplantation of huPBLs into NOD-SCID mice increased reconstitution of human T lymphocytes in a dose-dependent manner, with an optimal dosage of 1 microg/mouse. The number of human T lymphocytes (HLA-ABC+ CD3+) in the lymphoid organs or tissue of rhIL-15-treated huPBL-NOD-SCID mice increased 11- to 80-fold, and phytohemagglutinin-induced T-lymphocyte proliferation and cytokine production were significantly enhanced. Additionally, although mature human cells have not been thought to enter the murine thymus, human T lymphocytes were detected in the huPBL-NOD-SCID thymus after rhIL-15 treatment. Thus, rhIL-15 can be used to optimize long-term peripheral T-cell engraftment in these human-mouse chimeras and may also be useful in clinical treatment of T-cell deficiencies.

Animals↗

PubMed2006

[Methylation status of the 5' CpG islands in FHIT gene in the plasma and tissues of cervical cancer patients].

To evaluate the methylation status of the 5' CpG islands in FHIT gene using plasma and tissue samples from cervical cancer patients and find a novel marker for non-invasive diagnosis of cervical cancer, methylation-specific PCR (MSP) was employed to examine CpG island methylation in FHIT gene in 151 pretreatment plasma samples and 30 tumor tissue samples obtained from cervical cancer patients. MSP product was cloned and sequenced directly. CpG island methylation of FHIT was detected in 31.13% of the plasma samples, and in 53.33% of the tissue samples. The total concordant rate of methylation status between plasma and tissue samples in FHIT gene was 80.00%. We found a strong positive correlation between FHIT methylation in the plasma and the clinical stage and histological grade of the tumor. The data showed that CpG island methylation of the FHIT gene is prevalent in the plasma and tissue samples from cervical cancer patients. FHIT detection may be used as a non-invasive marker for diagnosis of cervical cancer and prognostic treatment evaluation.

Acid Anhydride Hydrolases↗

PubMed2006

[Synthesis and characterizations of poly (ethylene glycol)-block-poly (glutamate)].

Amine-terminated poly (ethylene glycol) (PEG) was prepared by two steps. Firstly, potassium naphthalene was added to a solution of methoxypolyethylene glycol 5,000 in benzene until the solution maintains green in half of an hour, then excess tosylchloride was introduced; secondly, the conversion of the tosylate into an amine was carried out by Gabriel synthesis. The block copolymer poly (ethylene glycol)-co-poly (gamma-benzyl L-glutamate ) could be obtained by ring-opening polymerization of gamma-benzyl-L-glutamate N-carboxy anhydride with amine-terminated PEG as macroinitiator. And the benzyl group could be removed by sodium hydroxide. The product structure was characterized by IR, 1HNMR, GPC. The cisplatin-loaded micelle was observed by transmission electron microscope (TEM). And the block copolymer is expected to be useful as functional materials including carrier systems in drug controlled delivery applications.

Drug Carriers↗

PubMed2006

[Methylation status of FHIT gene in plasma and expression of FHIT gene in cancer tissue of cervical cancer patients].

OBJECTIVE: To explore the methylation status of 5' CpG island of fragile histidine triad (FHIT) gene in plasma and the expression of FHIT protein in cancer tissue of cervical cancer patients. METHODS: Methylation-specific PCR (MS-PCR) was employed to examine methylation of FHIT gene in 151 plasma samples before treatment. The immunohistochemistry was used to the expression of FHIT protein in cancer tissues. RESULTS: CpG island methylation of FHIT was detected in 31.13% of plasma samples. The expression of FHIT protein was decreased or discarded in 59.60% of cervical cancer tissues. Among them 47.78% was included in methylation positive samples. CONCLUSION: CpG island methylation of FHIT gene in plasma plays an important role on cervical cancer, which results in decreased expression of FHIT protein. It can be used to diagnose and evaluate the effect of treatment to cervical cancers.

Acid Anhydride Hydrolases↗

PubMed2005

Toll-like receptor 3 ligand attenuates LPS-induced liver injury by down-regulation of toll-like receptor 4 expression on macrophages.

This study demonstrates that pretreatment with polyinosinic-polycytidylic acid (poly I:C) significantly decreased the mortality and liver injury caused by injection of lipopolysaccharide (LPS) in the presence of d-galactosamine (d-GalN) in C57BL/6 mice. Depletion of natural killer, natural killer T, and T cells did not change the protective effect of poly I:C on LPS/d-GalN-induced liver injury in vivo. However, depletion of macrophages abolished LPS/d-GalN-induced fulminant hepatitis, which could be restored by adoptive transfer of macrophages but not by transfer of poly I:C-treated macrophages. Treatment with poly I:C down-regulated the expression of the toll-like receptor 4 (TLR4) on macrophages and reduced the sensitivity of macrophages (Kupffer cells and peritoneal macrophages from C57BL/6 mice, or RAW264.7 cells) to LPS stimulation. Poly I:C pretreatment also impaired the signaling of mitogen-activated protein kinases and NF-kappaB induced by LPS in RAW264.7 cells. Blockade of TLR3 with a TLR3 antibody abolished poly I:C down-regulation of TLR4 expression and LPS stimulation of TNF-alpha production in RAW264.7 cells. Taken together, our findings suggest that activation of TLR3 by its ligand, poly I:C, induced LPS tolerance by down-regulation of TLR4 expression on macrophages.

Animals↗